Search Results (95)

In response to the urgent need for innovative fungicides to ensure food security and safety, a series of twenty-three novel trifluoromethylpyridine compounds were designed and synthesized using a scaffold hopping strategy derived from dehydrozingerone. This approach involved converting the α, β-unsaturated ketone moiety into a pyridine ring. Bioassay results indicated that the majority of these compounds exhibited promising in vitro antifungal activity, particularly against Rhizoctonia solani and Colletotrichum musae. Notably, compound 17 showed the highest efficacy and broad-spectrum activity, with median effective concentrations (EC₅₀) ranging from 2.88 to 9.09 μg/mL. Phenoxytrifluoromethylpyridine derivatives, including compound 17, exhibited superior antifungal activity compared to benzyloxytrifluoromethylpyridine derivatives. In vivo tests revealed that both compounds 17 and 23 exhibited moderate control effects against C. musae. The degradation half-lives of compounds 17 and 23 in bananas were determined to be 176.9 h and 94.8 h, respectively, indicating the stability of their structures in the environment. Molecular docking studies indicated that compound 23 interacts with succinate dehydrogenase, offering valuable insights for the structural optimization of compound 23. Full article

The phytochemical profile and antioxidant activities of Prunus africana bark, Leea indica and Paullinia pinnata leaves from Cameroon were investigated in this study. The yields of pure methanolic extraction were 11.9%, 11.1% and 10.8% in P. africana bark, L. indica and P. pinnata leaves, respectively. The total phenolic content was 189.0 ± 16.93, 163.6 ± 14.73 and 114.6 ± 10.38 mg GAE/g and total flavonoid content was 43.25 ± 6.43, 28.31 ± 4.44, and 19.75 ± 4.03 mg RU/g in P. africana bark, L. indica and P. pinnata leaves, respectively. The antioxidant activities of the plants were evaluated by DPPH, ABTS and FRAP assays. The IC₅₀ evaluated in P. africana bark, L. indica and P. pinnata leaves was 109.5 ± 13.2, 132.1 ± 18.7 and 156.1 ± 21.9 µg/mL for DPPH and 98.1 ± 4.8, 101.3 ± 12.1 and 133.9 ± 16.0 µg /mL for ABTS assay. The FRAP value was 61.1 ± 1.5, 50.5 ± 1.5 and 43.4 ± 2.1 µMFe²⁺/g in the same sequence. The functional groups for the corresponding phytochemicals, including alkane, alkene, aliphatic ether, ester, amine, α, β-unsaturated ester, alcohol, phenol, carboxylic acid, and aliphatic ketone, were identified through fourier-transform infrared analysis. The identified and quantified phenolic acids in this study were methyl-4-hydroxybenzoic, caffeic, protocatechuic and p-coumaric acid, identified using high-performance liquid chromatography. Full article

Background/Objectives: Microcolins A–M are cytotoxic marine lipopeptides produced by the cyanobacterium Moorena producens, also known as Lyngbya majuscula. Recent studies have shown that two compounds in the series, microcolins B and H, can form covalent complexes with phosphatidylinositol transfer proteins α and β (PITPα/β) upon the reaction of their α,β-unsaturated ketone group with the thiol group of a key cysteine residue of PITP. These observations prompted us to compare the binding of all microcolins and a few related derivatives (VT01454 and (deoxy)majusculamide D) to PITP to delineate structure–binding relationships. Methods: A molecular docking analysis led to the identification of microcolin E as the potentially best PITPα binder in the series, followed by microcolins B and H and analog VT01454. The computational data agree well with the published experimental results. Results: The binding of microcolin H into a large cavity of PITPα positions its reactive electrophilic α,β-unsaturated ketone close to the thiol of Cys95, enabling the facile formation of a covalent C-S linkage. A similar bonding can occur with the Cys94 of PITPβ. Molecular models of microcolins bound to PITP were compared to identify structural elements chiefly implicated in the recognition process. Conclusions: This computational study provides guidance in the design of microcolin derivatives targeting PITPα/β considered targets for cancer and inflammatory pathologies. Full article

Human lactate dehydrogenase A (hLDHA) is a homotetrameric isozyme involved in the conversion of glyoxylate into oxalate in the cytosol of liver cells (hepatocytes) and partially responsible for the overproduction of oxalate in patients with the rare disease called primary hyperoxaluria (PH). Recently, hLDHA inhibition has been validated as a safe therapeutic method to try to control the PH disease. Stiripentol (STP) is an approved drug used in the treatment of seizures associated with Dravet’s syndrome (a severe form of epilepsy in infancy) which, in addition, has been drawing interest in recent years also for potentially treating PH, due to its hLDHA inhibitory activity. In this work, several new STP-related compounds have been synthesized and their hLDHA inhibitory activity has been compared to that of STP. The synthesis of these analogues to STP was accomplished using crossed-aldol condensation guided by lithium enolate chemistry and a successive regioselective reduction of the resulting α,β-unsaturated ketones. The target molecules were obtained as racemates, which were separated into their enantiomers by chiral HPLC. The absolute configurations of pure enantiomers were determined by the modified Mosher’s method and electronic circular dichroism (ECD) spectroscopy. For the inhibitory effect over the hLDHA catalytic activity, a kinetic spectrofluorometric assay was used. All the new synthesized compounds turned out to be more active at 500 μM (46–72% of inhibition percentage) than STP (10%), which opens a new line of study on the possible capacity of these analogues to reduce urinary oxalate levels in vivo more efficiently. Full article

The present article describes the successful performance of crossed aldol reactions of the CF₃-containing pseudo-C₂ symmetric cyclic imide with various aldehydes. The utilization of HMPA as an additive attained the preferential formation of the anti-products in good to excellent yields, which contrasts with our previous method without this additive, proceeding to furnish the corresponding syn-isomers. The effective participation of ketones and α,β-unsaturated carbonyl compounds in reactions with this imide was also demonstrated to expand the application of this imide. Full article

A novel and controllable synthesis of thioacetals/thioketals and β-sulfanyl ketones mediated by the reaction of aldehyde/acetone with thiols has been developed. In this protocol, β-sulfanyl ketones can be generated without the prior preparation of α, β-unsaturated carbonyl compounds. A variety of thiols reacted with aldehyde/acetone and provided the corresponding thioacetals/thioketals and β-sulfanyl ketones in good to excellent yields, respectively. This protocol is operationally simple, mild, and atom-economical, providing controllable access to thioacetals/thioketals and thia-Michael addition products under mild conditions. Full article

The coastal region of the Caribbean is notable for the chemical diversity found in its sponge products, resulting in the biosynthesis of a range of natural marine products, including polyketides. The objective of this manuscript is to summarize the isolated polyketides from sponges of the genus Plakortis located around the Caribbean coasts. This review provides a comprehensive overview of specimen location, isolation procedures, characterization methods, and biological assay studies of about 95 polyketides isolated from 1978 to 2024 in the Caribbean coasts of The Bahamas, Cayman Islands, Belize, Dominica, Jamaica, Martinique, Panamá, Puerto Rico, and Tobago. The Caribbean polyketides have been isolated from different types of Plakortis sp., such as P. simplex, P. halichondroides, P. zyggompha, and P. angulospiculatus, which have demonstrated antimicrobial, anticancer, anti-inflammatory, antiparasitic, and antiviral activities. A variety of linear polyketides with different functionalities have been reported, including endoperoxides (1,2-dioxane), lactones, indane-type bicyclics (spiculane and zyggomphic), alcohols, alkenes, styryl groups, α,β-unsaturated carboxylic acids, and ketones, as well as related natural products of biosynthetic origin. The aim is to encourage further exploration by researchers in the Caribbean’s coastal marine environments, promoting the discovery and investigation of novel polyketide cyclic peroxides and related secondary metabolites to identify additional bioactive medicinal natural products. Full article

4′-dihydrochalcones are secondary metabolites isolated from many medicinal plants and from the resin known as ‘dragon’s blood’. Due to their biological potential, our research objective was to determine the possibilities of using biocatalysis processes carried out in deep eutectic solvents (DESs) to obtain 4′-dihydrochalcones as a model compound. The processes were carried out in a culture of the yeast Yarrowia lipolytica KCh 71 and also in cultures of strains of the genera Rhodotorula and Debaryomyces. Based on the experiments carried out, an optimum process temperature of 35 °C was chosen, and the most suitable DES contained glycerol as a hydrogen bond donor (HBD). For a medium with 30% water content (DES 11), the conversion observed after 24 h exceeded 70%, while increasing the amount of water to 50% resulted in a similar level of conversion after just 1 h. A fivefold increase in the amount of added substrate resulted in a reduction in conversion, which reached 30.3%. Of the other yeast strains tested, Rhodotorula marina KCh 77 and Rhodotorula rubra KCh 4 also proved to be good biocatalysts for the bioreduction process. For these strains, the conversion reached 95.4% and 95.1%, respectively. These findings highlight the potential of yeast as a biocatalyst for the selective reduction of α,β-unsaturated ketones and the possibility of using a DESs as a reaction medium in this process. Full article

Chalcone (1,3-diaryl-2-propen-1-one) is an α, β-unsaturated ketone that serves as an active constituent or precursor of numerous natural substances, exhibiting a broad spectrum of pharmacological effects. In this study, the classical Claisen–Schmidt condensation method was used to synthesize the chalcone derivative 2′,4′-dimethoxychalcone (DTC) and evaluate its pharmacological activity. By upregulating the expression of the epithelial cell marker E-cadherin and downregulating the expression of the mesenchymal cell marker vimentin, DTC was found to inhibit transforming growth factor-β1 (TGF-β1)-induced epithelial–mesenchymal transition (EMT) process in A549 cells, maintaining the cells’ epithelial-like morphology and reducing the ability of the cells to migrate. Additionally, DTC demonstrated the ability to decrease the expression levels of nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in RAW264.7 cells, suggesting a possible anti-inflammatory effect. Furthermore, DTC was found to exhibit bacteriostatic activity against Staphylococcus aureus (S. aureus), Proteus vulgaris (P. vulgaris), methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans (C. albicans), indicating that this chemical may possess broad-spectrum antibacterial activity. Full article

Many biological functions of curcumin have been reported. As certain bioactivities of curcumin are eliminated by antioxidants, reactive oxygen species generated by curcumin have been suggested as a relevant mechanism. In the present study, the effects of different types of antioxidants on the stability and bioactivities of curcumin were analyzed. High concentrations (>4 mM) of thiol antioxidants, including N-acetylcysteine (NAC), glutathione (GSH), and β-mercaptoethanol, accelerated the decomposition of curcumin and other curcuminoids; the submillimolar levels (<0.5 mM) of GSH and NAC rather improved their stability. Ascorbic acid or superoxide dismutase also stabilized curcumin, regardless of their concentration. The cellular levels and bioactivities of curcumin, including its cytotoxicity and the induction of heme oxygenase-1, were significantly reduced in the presence of 8 mM of GSH and NAC. The effects were enhanced in the presence of submillilmolar GSH and NAC, or non-thiol antioxidants. The present results indicate that antioxidants with a reduced thiol group could directly interact with the α,β-unsaturated carbonyl moiety of curcuminoids and modulate their stability and bioactivity. Full article

Heterocyclic derivatives of hormones have attracted great interest as a privileged scaffold for drug discovery due to their outstanding biological activity. A number of them are potent anticancer agents which are used in the chemotherapy of breast and prostate cancers. Here, the data obtained by the authors in the field of studying functionalized thiohydrazides as simple “versatile agents” for the installation of heterocyclic moiety to the steroid core are summarized. Namely, a flexible synthetic approach to unknown pyrazolines, 1,3,4-thiadiazole, thiadiazine, and pyridazine derivatives of steroids with selective control of heterocyclization patterns are discussed. Steroidal 1,3,4-thiadiazoles were obtained via the oxidative heterocyclization of oxamic acid thiohydrazides with 16-hydroxymethylidene-∆^1,3,5(10)-estratrieno-17-one. An extension of this reaction to steroidal α,β-unsaturated ketones resulted in androst-5-ene-[17,16d]-pyrazolines. Spiro-androstene-17,6′[1′,3′,4′]thiadiazines were exclusively synthesized employing 16β,17β-epoxypregnenolone. Using 21-bromopregna-5,16-dien-20-one as a substrate, 17-[1′,3′,4′]thiadiazine-substituted androstenes were prepared. 18-Nor-5α-androsta-2,13-diene[3,2-d]pyridazines, androsta-2-ene[3,2-d]pyridazines and ∆^1,3,5(10)-estratrieno[16,17-d]pyridazines were synthesized via two steps involving the Vilsmeier–Haack reaction of enolizable steroidal ketones, giving chlorovinyl aldehydes, followed by the imination of the former with oxamic acid thiohydrazides. The antiproliferative activity of the synthesized compounds against breast and prostate cancer cell lines, along with lead compounds’ in-depth characterization, are included. The lead compounds were found to have potent selectivity and, in some cases, a significant effect on the signaling pathways in parental and 4-hydroxytamoxifen-resistant cells. Full article

An efficient, economical, and green, sustainable synthesis of fused azines using Mg-Al hydrotalcite under a high-pressure Q-Tube reactor has been developed. This reaction proceeds through the aza-Michael addition of α,β-unsaturated ketone with different aminoazoles. This method offered excellent yields in a short reaction time that economically saved energy in addition to the protocol showing the reuse of the catalyst seven times without losing its catalytic activity. Full article

Recent studies have demonstrated the antiproliferative and cytotoxic effects of aza-steroids and steroidal sapogenins on human cancer cell lines. The scientific community has shown a growing interest in these compounds as drug candidates for cancer treatment. In the current work, we report the synthesis of new diosgenin oxime derivatives as potential antiproliferative agents. From (25 R)-5α-spirost-3,5,6-triol (1), a diosgenin derivative, ketones 2, 3, 4, and 9 were obtained and used as precursors of the new oximes. A condensation reaction was carried out between the steroidal ketones (2, 3, 4, and 9) with hydroxylamine hydrochloride in 2,4,6-trimethylpyridine to produce five spirostanic oximes (four of them are not reported before) with a 42–96% yield. Also, a new spirostanic α, β-unsaturated cyanoketone was synthesized via Beckmann fragmentation using thionyl chloride with a 62% yield. Furthermore, we proposed a reaction mechanism with the aim of explaining such transformation. Full article

As an important cancer therapeutic target, extracellular signal-regulated kinases (ERK) are involved in triggering various cellular responses in tumors. Regulation of the ERK signaling pathway by the small molecular inhibitors is highly desired for the sake of cancer therapy. In contrast to the routine inhibitors targeting ERKs through long-range non-bonding interactions, Ponatinib, a covalent inhibitor to ERK2 with a macrocyclic structure characterized by the α,β-C=C unsaturated ketone, can form the stable -C(S)-C(H)-type complex via the four-center barrier due to the nucleophilic addition reaction of the thiol group of the Cys166 residue of ERK2 with the C=C double bond of Ponatinib with reaction free-energy barrier of 47.2 kcal/mol. Reaction mechanisms for the covalent binding were calculated using QM/MM methods and molecular dynamics simulations. The interaction modes and the corresponding binding free energies were obtained for the non-covalent and covalent complexation. The binding free energies of the non-covalent and covalent inhibitions are 14.8 kcal/mol and 33.4 kcal/mol, respectively. The mechanistic study stimulated a rational design on the modified Ponatinib structure by substituting the C=C bond with the C=N bond. It was demonstrated that the new compound exhibits better inhibition activity toward ERK2 in term of both thermodynamic and kinetic aspects through the covalent binding with a lower reaction free-energy barrier of 23.1 kcal/mol. The present theoretical work sheds new light on the development of the covalent inhibitors for the regulation of ERKs. Full article

Chalcones are α,β-unsaturated ketones with great structural diversity and various applications. A chalcone produced by condensation of 2-acetylpyridine with 2-naphthaldehyde (L) was employed for synthesis of two mononuclear complexes: [Eu(L)(hfac)₃(H₂O)]·0.5CHCl₃ and [Tb(L)(hfac)₃], where hfac is the hexafluoroacetylacetonate anion. The chalcone and complexes were structurally characterized by single-crystal X-ray diffraction. The chalcone acts as a chelating bidentate ligand. Luminescent properties of the ligand L and the complexes were investigated in the solid state. For these heteroleptic mononuclear complexes, the emission of the Eu(III) and Tb(III) ions was influenced by the excitation wavelength. Full article